Structural variants of human growth hormone: biochemical, genetic, and clinical aspects

Abstract

Human growth hormone (hGH) is a mixture of peptides in which the major physiologic component is a single chain polypeptide of 191 residues with a molecular weight of 22,000 ("22K" form). The minor components differ from the 22K form in terms of mass (e.g. the 20K form, a single-chain peptide synthesized by deletion of residues 32-46 of the 22K isomer, and the 45K variant formed by aggregation of the 22K molecule), or of charge (e.g. the more acidic two-chain forms alpha 2 and alpha 3 which are generated by proteolytic deletion of residues 135-140 and 135-146 from the 22K variant). The minor components also differ from the 22K molecule in (a) their metabolic effects; (b) their capacity to bind to antiserum raised against the 22K form in a radioimmunoassay (RIA); and (c) their ability to bind to membrane receptors for the 22K hGH in a radioreceptor assay (RRA). Two genes, N and V, involved in the biosynthesis of hGH, are located on human chromosome 17. Heritable alterations of the N gene may cause deficiency of immunoreactive hGH and growth failure. A pathologic variant of hGH has also been identified which is indistinguishable from the 22K form on RIA, but which has low reactivity on hGH-RRA and low somatomedogenic activity. Several mechanisms to account for this bioinactive variant are discussed.